Mycophenolate mofetil
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Identification
- Summary
Mycophenolate mofetil is an inosine monophosphate dehydrogenase inhibitor used to prevent the rejection of kidney, heart, or liver transplants.
- Brand Names
- Cellcept, Myfenax, Myhibbin
- Generic Name
- Mycophenolate mofetil
- DrugBank Accession Number
- DB00688
- Background
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH).3 This drug is an immunosuppressant combined with drugs such as Cyclosporine and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants.13 It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995.6 In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis.2,3
Previously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity.6 The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 433.4947
Monoisotopic: 433.210052351 - Chemical Formula
- C23H31NO7
- Synonyms
- 2-morpholinoethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate
- Mycophenolate mofetil
- Mycophenolic acid morpholinoethyl ester
- External IDs
- 168396
- RS 61443
- RS-61443
Pharmacology
- Indication
Mycophenolate mofetil is indicated in combination with other immunosuppressants to prevent the rejection of kidney, heart, or liver transplants in adult and pediatric patients ≥3 months old.15 Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy.4 Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in prevention of Transplanted organ rejection •••••••••••• •••••• ••••••••• •••••••• •••••••••• ••••••••••• •••••• Adjunct therapy in prevention of Transplanted organ rejection •••••••••••• •••••• ••••••••• •••••••• •••••••••• ••••••••••• •••••• Adjunct therapy in prevention of Transplanted organ rejection •••••••••••• •••••• ••••••••• •••••••• •••••••••• ••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection.3 The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection.
- Mechanism of action
The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA.9 MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine 5’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II.6 IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP).2,3,5 GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production.6 Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.12
Target Actions Organism AProstaglandin E2 receptor EP2 subtype modulatorHumans AInosine-5'-monophosphate dehydrogenase 1 inhibitorinducerHumans AInosine-5'-monophosphate dehydrogenase 2 inhibitorHumans U6-pyruvoyl tetrahydrobiopterin synthase inhibitorHumans - Absorption
Mycophenolate mofetil is rapidly absorbed in the small intestine.13,10 The maximum concentration of its active metabolite, MPA, is attained 60 to 90 minutes following an oral dose.6 The average bioavailability of orally administered mycophenolate mofetil in a pharmacokinetic study of 12 healthy patients was 94%. In healthy volunteers, the Cmax of mycophenolate mofetil was 24.5 (±9.5)μg/mL.13 In renal transplant patients 5 days post-transplant, Cmax was 12.0 (±3.82) μg/mL, increasing to 24.1 (±12.1)μg/mL 3 months after transplantation. AUC values were 63.9 (±16.2) μg•h/mL in healthy volunteers after one dose, and 40.8 (±11.4) μg•h/mL, and 65.3 (±35.4)μg•h/mL 5 days and 3 months after a renal transplant, respectively.13 The absorption of mycophenolate mofetil is not affected by food.6
- Volume of distribution
The volume of distribution of mycophenolate mofetil is 3.6 (±1.5) to 4.0 (±1.2) L/kg.13
- Protein binding
The protein binding of mycophenolic acid, the metabolite of mycophenolate mofetil, is 97%13 and it is mainly bound to albumin.6 MPAG, the inactive metabolite, is 82% bound to plasma albumin at normal therapeutic concentrations. At elevated MPAG concentrations due to various reasons, including renal impairment, the binding of MPA may be decreased due to competition for binding.13
- Metabolism
After both oral and intravenous administration mycophenolate mofetil is entirely metabolized by liver carboxylesterases 1 and 2 to mycophenolic acid (MPA), the active parent drug. It is then metabolized by the enzyme glucuronyl transferase, producing the inactive phenolic glucuronide of MPA (MPAG).13 The glucuronide metabolite is important, as it is then converted to MPA through enterohepatic recirculation. Mycophenolate mofetil that escapes metabolism in the intestine enters the liver via the portal vein and is transformed to pharmacologically active MPA in the liver cells.10N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide portion of N-(2-hydroxyethyl)-morpholine are additional metabolites of MMF occurring in the intestine as a result of liver carboxylesterase 2 activity.10,13 UGT1A9 and UGT2B7 in the liver are the major enzymes contributing to the metabolism of MPA in addition to other UGT enzymes, which also play a role in MPA metabolism. The four major metabolites of MPA are 7-O-MPA-β-glucuronide (MPAG, inactive), MPA acyl-glucuronide (AcMPAG), produced by uridine 5ʹ-diphosphate glucuronosyltransferases (UGT) activities, 7-O-MPA glucoside produced via UGT, and small amounts 6-O-des-methyl-MPA (DM-MPA) via CYP3A4/5 and CYP2C8 enzymes.6
Hover over products below to view reaction partners
- Route of elimination
A small amount of drug is excreted as MPA in the urine (less than 1%). When mycophenolate mofetil was given orally in a pharmacokinetic study, it was found to be 93% excreted in urine and 6% excreted in feces. Approximately 87% of the entire administered dose is found to be excreted in the urine as MPAG, an inactive metabolite.6,13
- Half-life
The average apparent half-life of mycophenolate mofetil is 17.9 (±6.5) hours after oral administration and 16.6 (±5.8) hours after intravenous administration.13
- Clearance
Plasma clearance of mycophenolate mofetil is 193 mL/min after an oral dose and 177 (±31) mL/min after an intravenous dose.13
- Adverse Effects
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- Toxicity
LD50
The LD50 of oral mycophenolate mofetil in rats is 250 mg/kg and >4000 mg/kg in mice.14
Overdose information
Possible signs and symptoms of acute overdose may consist of hematological abnormalities including leukopenia and neutropenia, and gastrointestinal symptoms.6,7,8
- Pathways
Pathway Category Mycophenolic Acid Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Mycophenolate mofetil may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Mycophenolate mofetil can be increased when it is combined with Abametapir. Abatacept The metabolism of Mycophenolate mofetil can be increased when combined with Abatacept. Abemaciclib Abemaciclib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level. Abiraterone The metabolism of Mycophenolate mofetil can be decreased when combined with Abiraterone. - Food Interactions
- Avoid multivalent ions. Take multivalent ions such as calcium, iron, or magnesium at least 2 hours after taking this medication.
- Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Mycophenolate mofetil hydrochloride UXH81S8ZVB 116680-01-4 OWLCGJBUTJXNOF-HDNKIUSMSA-N - Active Moieties
Name Kind UNII CAS InChI Key Mycophenolic acid prodrug HU9DX48N0T 24280-93-1 HPNSFSBZBAHARI-RUDMXATFSA-N - Product Images
- International/Other Brands
- CellCept Oral Suspension (Genentech USA, Inc.) / CellCept Intravenous (Genentech USA, Inc.)
- Brand Name Prescription Products
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Accel-mycophenolate Mofetil Capsules Capsule 250 mg Oral Accel Pharma Inc Not applicable Not applicable Canada Accel-mycophenolate Mofetil Tablets Tablet 500 mg Oral Accel Pharma Inc Not applicable Not applicable Canada Ach-mycophenolate Tablet 500 mg Oral Accord Healthcare, S.L.U. 2012-02-16 Not applicable Canada Ach-mycophenolate Powder, for suspension 200 mg / mL Oral Accord Healthcare, S.L.U. Not applicable Not applicable Canada Ach-mycophenolate Capsule 250 mg Oral Accord Healthcare, S.L.U. 2012-05-01 Not applicable Canada
Categories
- Drug Categories
- Agents Causing Muscle Toxicity
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibiotics, Antineoplastic
- Antibiotics, Antitubercular
- Antimetabolite Immunosuppressant
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Fatty Acids
- Immunologic Factors
- Immunosuppressive Agents
- IMP Dehydrogenase, antagonists & inhibitors
- Lipids
- Mycophenolic Acid and Prodrugs
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 substrates
- P-glycoprotein substrates
- UGT1A1 Substrates
- UGT1A6 substrate
- UGT1A9 Substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phthalides. These are compounds containing a 3-hydrocarbylidene-2-benzofuran-1(3H)-one moiety,.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Isocoumarans
- Sub Class
- Isobenzofuranones
- Direct Parent
- Phthalides
- Alternative Parents
- Anisoles / Alkyl aryl ethers / Fatty acid esters / Morpholines / Dicarboxylic acids and derivatives / Vinylogous acids / Trialkylamines / Amino acids and derivatives / Lactones / Carboxylic acid esters show 7 more
- Substituents
- Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, carboxylic ester, phenols, ether, gamma-lactone (CHEBI:8764)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 9242ECW6R0
- CAS number
- 128794-94-5
- InChI Key
- RTGDFNSFWBGLEC-SYZQJQIISA-N
- InChI
- InChI=1S/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3/b15-4+
- IUPAC Name
- 2-(morpholin-4-yl)ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
- SMILES
- COC1=C(C\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C
References
- Synthesis Reference
Roger C. Fu, De-Mei Leung, Jeffrey S. Fleitman, Michele C. Rizzolio, Andrew R. Miksztal, "Process for preparing pharmaceutical compositions containing crystalline anhydrous mycophenolate mofetil salts." U.S. Patent US5545637, issued November, 1988.
US5545637- General References
- Picard N, Cresteil T, Premaud A, Marquet P: Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit. 2004 Dec;26(6):600-8. [Article]
- Villarroel MC, Hidalgo M, Jimeno A: Mycophenolate mofetil: An update. Drugs Today (Barc). 2009 Jul;45(7):521-32. doi: 10.1358/dot.2009.45.7.1384878. [Article]
- Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2-8. [Article]
- Santiago P, Schwartz I, Tamariz L, Levy C: Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis. Aliment Pharmacol Ther. 2019 Apr;49(7):830-839. doi: 10.1111/apt.15157. Epub 2019 Feb 13. [Article]
- Sagcal-Gironella AC, Fukuda T, Wiers K, Cox S, Nelson S, Dina B, Sherwin CM, Klein-Gitelman MS, Vinks AA, Brunner HI: Pharmacokinetics and pharmacodynamics of mycophenolic acid and their relation to response to therapy of childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum. 2011 Feb;40(4):307-13. doi: 10.1016/j.semarthrit.2010.05.007. Epub 2010 Jul 23. [Article]
- Park H: The emergence of mycophenolate mofetilin dermatology: from its roots in the world of organ transplantation to its versatile role in the dermatology treatment room. J Clin Aesthet Dermatol. 2011 Jan;4(1):18-27. [Article]
- Alex R, Mathew M, Arul S, Kundavaram A: Overdose of mycophenolate mofetil managed in a secondary care hospital in South India. Indian J Pharmacol. 2014 May-Jun;46(3):337-8. doi: 10.4103/0253-7613.132191. [Article]
- Parfitt JR, Jayakumar S, Driman DK: Mycophenolate mofetil-related gastrointestinal mucosal injury: variable injury patterns, including graft-versus-host disease-like changes. Am J Surg Pathol. 2008 Sep;32(9):1367-72. [Article]
- Allison AC, Eugui EM: Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant. 1996 Feb;10(1 Pt 2):77-84. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Sherwin CM, Fukuda T, Brunner HI, Goebel J, Vinks AA: The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24. doi: 10.2165/11536640-000000000-00000. [Article]
- Srinivas TR, Kaplan B, Meier-Kriesche HU: Mycophenolate mofetil in solid-organ transplantation. Expert Opin Pharmacother. 2003 Dec;4(12):2325-45. doi: 10.1517/14656566.4.12.2325 . [Article]
- FDA label, Mycophenolate mofetil [Link]
- MSDS, Mycophenolate mofetil [Link]
- FDA Approved Drug Products: Cellcept (mycophenolate mofetil) for oral or intravenous administration [Link]
- External Links
- Human Metabolome Database
- HMDB0014826
- KEGG Drug
- D00752
- KEGG Compound
- C07908
- PubChem Compound
- 5281078
- PubChem Substance
- 46505626
- ChemSpider
- 4444535
- BindingDB
- 50248299
- 68149
- ChEBI
- 8764
- ChEMBL
- CHEMBL1456
- ZINC
- ZINC000021297660
- Therapeutic Targets Database
- DNC000397
- PharmGKB
- PA450566
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Mycophenolic_acid
- FDA label
- Download (200 KB)
- MSDS
- Download (82.3 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Treatment Allografts / Lung Transplant 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment End Stage Renal Disease (ESRD) 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Haemoglobinopathies congenital / Sickle Cell Disease (SCD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Acute Transplant Rejection in Patients Receiving Allogeneic Renal Transplant 1 somestatus stop reason just information to hide Not Available Completed Not Available Autoimmune Disorder / Neurological Disorders 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Roche palo alto llc
- Accord healthcare inc usa
- Apotex corp
- Endo pharmaceuticals inc
- Mylan pharmaceuticals inc
- Roxane laboratories inc
- Sandoz inc
- Strides arcolab ltd
- Teva pharmaceuticals usa
- Zydus pharmaceuticals usa inc
- Accord healthcare inc
- Apotex inc
- Packagers
- Accord Healthcare
- Amerisource Health Services Corp.
- Apotex Inc.
- Cadila Healthcare Ltd.
- Cardinal Health
- Chunghwa Chemical Synthesis and Biotech Co. Ltd.
- Endo Pharmaceuticals Inc.
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Intas Pharmaceuticals Ltd.
- JHP Pharmaceuticals LLC
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Legacy Pharmaceuticals Packaging LLC
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Poli Industria Chimica SPA
- Rebel Distributors Corp.
- Roxane Labs
- Sandoz
- Syntex SA
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Solution Intravenous 500.00 mg Tablet Oral 500.00 mg Tablet Oral 250.00 mg Capsule Oral 250 mg/1 Injection, powder, lyophilized, for solution Intravenous 500 mg/20mL Powder, for suspension Oral 1 g/5ml Powder, for suspension Oral 200 mg / mL Tablet Oral 500 mg Tablet, film coated Oral 500 mg/1 Tablet, coated Oral 500 mg Injection, solution Intravenous 500 mg Injection, powder, for solution Intravenous 500 mg Powder, for solution Intravenous 500 mg / vial Tablet Oral 250.000 mg Tablet, delayed release Oral Tablet Oral 500.0 mg Capsule Oral 250 mg Tablet, film coated Oral Capsule Oral Tablet Oral Tablet, film coated Oral 250 mg Capsule, gelatin coated Oral 250 mg Powder, for suspension Oral 200 mg/1mL Tablet Oral 500 mg/1 Tablet, coated Oral 500 mg/1 Tablet, film coated Oral 500 mg Injection, powder, for solution Parenteral 500 mg Tablet, delayed release Oral 180 MG Tablet, delayed release Oral 360 MG Suspension Oral 200 mg/1mL Capsule Oral 250.000 mg Tablet Oral 500.000 mg Injection, powder, lyophilized, for solution Intravenous 500 mg/1vial - Prices
Unit description Cost Unit CellCept 200 mg/ml Suspension 175ml Bottle 875.84USD bottle Cellcept 500 mg vial 65.03USD vial Cellcept 500 mg tablet 10.43USD tablet Mycophenolate Mofetil 500 mg tablet 8.25USD tablet Mycophenolate 500 mg tablet 7.93USD tablet CellCept 250 mg capsule 5.21USD capsule Mycophenolate Mofetil 250 mg capsule 4.13USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5688529 No 1997-11-18 2014-11-18 US US5543408 No 1996-08-06 2013-09-15 US CA2172506 No 2007-07-17 2014-09-27 Canada CA1333285 No 1994-11-29 2011-11-29 Canada US11931455 No 2019-08-16 2039-08-16 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 93-94 https://pubchem.ncbi.nlm.nih.gov/compound/Mycophenolate-mofetil#section=Experimental-Properties boiling point (°C) 637.6±55.0 http://www.chemspider.com/Chemical-Structure.4444535.html water solubility 43 μg/mL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050722s021,050723s019,050758s019,050759s024lbl.pdf logP 2.5 http://www.hmdb.ca/metabolites/HMDB0014826 pKa 5.6 for the morpholino group and 8.5 for the phenolic group https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050722s021,050723s019,050758s019,050759s024lbl.pdf - Predicted Properties
Property Value Source Water Solubility 0.095 mg/mL ALOGPS logP 2.17 ALOGPS logP 3.47 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 9.76 Chemaxon pKa (Strongest Basic) 6.19 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 94.53 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 117.1 m3·mol-1 Chemaxon Polarizability 45.54 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8938 Blood Brain Barrier + 0.8594 Caco-2 permeable + 0.5904 P-glycoprotein substrate Substrate 0.8908 P-glycoprotein inhibitor I Inhibitor 0.8381 P-glycoprotein inhibitor II Inhibitor 0.8061 Renal organic cation transporter Inhibitor 0.5379 CYP450 2C9 substrate Non-substrate 0.8528 CYP450 2D6 substrate Non-substrate 0.602 CYP450 3A4 substrate Substrate 0.7646 CYP450 1A2 substrate Non-inhibitor 0.6878 CYP450 2C9 inhibitor Non-inhibitor 0.9155 CYP450 2D6 inhibitor Non-inhibitor 0.7684 CYP450 2C19 inhibitor Non-inhibitor 0.9122 CYP450 3A4 inhibitor Non-inhibitor 0.8316 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8664 Ames test Non AMES toxic 0.6484 Carcinogenicity Non-carcinogens 0.953 Biodegradation Not ready biodegradable 0.658 Rat acute toxicity 3.0412 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.771 hERG inhibition (predictor II) Non-inhibitor 0.7653
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 226.078366 predictedDarkChem Lite v0.1.0 [M-H]- 227.719866 predictedDarkChem Lite v0.1.0 [M-H]- 198.02019 predictedDeepCCS 1.0 (2019) [M-H]- 226.078366 predictedDarkChem Lite v0.1.0 [M-H]- 227.719866 predictedDarkChem Lite v0.1.0 [M-H]- 198.02019 predictedDeepCCS 1.0 (2019) [M+H]+ 224.998766 predictedDarkChem Lite v0.1.0 [M+H]+ 228.515566 predictedDarkChem Lite v0.1.0 [M+H]+ 200.57143 predictedDeepCCS 1.0 (2019) [M+H]+ 224.998766 predictedDarkChem Lite v0.1.0 [M+H]+ 228.515566 predictedDarkChem Lite v0.1.0 [M+H]+ 200.57143 predictedDeepCCS 1.0 (2019) [M+Na]+ 225.318466 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.132566 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.12022 predictedDeepCCS 1.0 (2019) [M+Na]+ 225.318466 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.132566 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.12022 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle
- Specific Function
- prostaglandin E receptor activity
- Gene Name
- PTGER2
- Uniprot ID
- P43116
- Uniprot Name
- Prostaglandin E2 receptor EP2 subtype
- Molecular Weight
- 39759.945 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorInducer
- General Function
- Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors
- Specific Function
- DNA binding
- Gene Name
- IMPDH1
- Uniprot ID
- P20839
- Uniprot Name
- Inosine-5'-monophosphate dehydrogenase 1
- Molecular Weight
- 55405.365 Da
References
- Bremer S, Rootwelt H, Bergan S: Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells. Clin Chem. 2007 Jun;53(6):1023-9. Epub 2007 Apr 26. [Article]
- Wang J, Yang JW, Zeevi A, Webber SA, Girnita DM, Selby R, Fu J, Shah T, Pravica V, Hutchinson IV, Burckart GJ: IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients. Clin Pharmacol Ther. 2008 May;83(5):711-7. Epub 2007 Sep 12. [Article]
- Sanquer S, Maison P, Tomkiewicz C, Macquin-Mavier I, Legendre C, Barouki R, Lang P: Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation. Clin Pharmacol Ther. 2008 Feb;83(2):328-35. Epub 2007 Aug 22. [Article]
- Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:7763314, PubMed:7903306). Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism (PubMed:14766016). It may also have a role in the development of malignancy and the growth progression of some tumors
- Specific Function
- DNA binding
- Gene Name
- IMPDH2
- Uniprot ID
- P12268
- Uniprot Name
- Inosine-5'-monophosphate dehydrogenase 2
- Molecular Weight
- 55804.495 Da
References
- Vannozzi F, Filipponi F, Di Paolo A, Danesi R, Urbani L, Bocci G, Catalano G, De Simone P, Mosca F, Del Tacca M: An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells from liver-transplant recipients. Transplant Proc. 2004 Nov;36(9):2787-90. [Article]
- Bremer S, Rootwelt H, Bergan S: Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells. Clin Chem. 2007 Jun;53(6):1023-9. Epub 2007 Apr 26. [Article]
- Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2-8. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin
- Specific Function
- 6-pyruvoyltetrahydropterin synthase activity
- Gene Name
- PTS
- Uniprot ID
- Q03393
- Uniprot Name
- 6-pyruvoyl tetrahydrobiopterin synthase
- Molecular Weight
- 16385.63 Da
References
- Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2-8. [Article]
- Allison AC, Eugui EM: Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118. [Article]
- Srinivas TR, Kaplan B, Meier-Kriesche HU: Mycophenolate mofetil in solid-organ transplantation. Expert Opin Pharmacother. 2003 Dec;4(12):2325-45. doi: 10.1517/14656566.4.12.2325 . [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:20610558, PubMed:23360619). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormone epiestradiol (PubMed:18719240). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558, PubMed:23360619). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A7
- Uniprot ID
- Q9HAW7
- Uniprot Name
- UDP-glucuronosyltransferase 1A7
- Molecular Weight
- 59818.315 Da
References
- Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A6
- Uniprot ID
- P19224
- Uniprot Name
- UDP-glucuronosyltransferase 1-6
- Molecular Weight
- 60750.215 Da
References
- Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P: Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos. 2005 Jan;33(1):139-46. Epub 2004 Oct 6. [Article]
- Sherwin CM, Fukuda T, Brunner HI, Goebel J, Vinks AA: The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24. doi: 10.2165/11536640-000000000-00000. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P: Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos. 2005 Jan;33(1):139-46. Epub 2004 Oct 6. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:16595710, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15472229, PubMed:16595710, PubMed:23288867). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens and estrogens (PubMed:15472229, PubMed:16595710, PubMed:18719240, PubMed:23288867). Produces dihydrotestosterone (DHT) diglucuronide from the DHT after two subsequent glucoronidation steps (PubMed:16595710). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A8
- Uniprot ID
- Q9HAW9
- Uniprot Name
- UDP-glucuronosyltransferase 1A8
- Molecular Weight
- 59741.035 Da
References
- Thervet E, Anglicheau D, Legendre C: [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:18719240, PubMed:23288867, PubMed:26220143). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A10
- Uniprot ID
- Q9HAW8
- Uniprot Name
- UDP-glucuronosyltransferase 1A10
- Molecular Weight
- 59809.075 Da
References
- Thervet E, Anglicheau D, Legendre C: [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
- Specific Function
- carboxylesterase activity
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- Fujiyama N, Miura M, Kato S, Sone T, Isobe M, Satoh S: Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate mofetil. Drug Metab Dispos. 2010 Dec;38(12):2210-7. doi: 10.1124/dmd.110.034249. Epub 2010 Sep 7. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Picard N, Cresteil T, Premaud A, Marquet P: Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit. 2004 Dec;26(6):600-8. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Picard N, Cresteil T, Premaud A, Marquet P: Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit. 2004 Dec;26(6):600-8. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Picard N, Cresteil T, Premaud A, Marquet P: Characterization of a phase 1 metabolite of mycophenolic acid produced by CYP3A4/5. Ther Drug Monit. 2004 Dec;26(6):600-8. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Not Available
- Specific Function
- carboxylic ester hydrolase activity
- Gene Name
- CES2
- Uniprot ID
- Q6IPK9
- Uniprot Name
- Carboxylic ester hydrolase
- Molecular Weight
- 64822.895 Da
References
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Fujiyama N, Miura M, Kato S, Sone T, Isobe M, Satoh S: Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate mofetil. Drug Metab Dispos. 2010 Dec;38(12):2210-7. doi: 10.1124/dmd.110.034249. Epub 2010 Sep 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- Miles KK, Kessler FK, Smith PC, Ritter JK: Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9. Epub 2006 Jun 21. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Miura M, Satoh S, Inoue K, Kagaya H, Saito M, Inoue T, Suzuki T, Habuchi T: Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9. Epub 2007 Sep 29. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Picard N, Yee SW, Woillard JB, Lebranchu Y, Le Meur Y, Giacomini KM, Marquet P: The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ther. 2010 Jan;87(1):100-8. doi: 10.1038/clpt.2009.205. Epub 2009 Nov 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Miura M, Satoh S, Inoue K, Kagaya H, Saito M, Inoue T, Suzuki T, Habuchi T: Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9. Epub 2007 Sep 29. [Article]
- Lamba V, Sangkuhl K, Sanghavi K, Fish A, Altman RB, Klein TE: PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9. doi: 10.1097/FPC.0000000000000010. [Article]
- Picard N, Yee SW, Woillard JB, Lebranchu Y, Le Meur Y, Giacomini KM, Marquet P: The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ther. 2010 Jan;87(1):100-8. doi: 10.1038/clpt.2009.205. Epub 2009 Nov 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Miura M, Kagaya H, Satoh S, Inoue K, Saito M, Habuchi T, Suzuki T: Influence of drug transporters and UGT polymorphisms on pharmacokinetics of phenolic glucuronide metabolite of mycophenolic acid in Japanese renal transplant recipients. Ther Drug Monit. 2008 Oct;30(5):559-64. doi: 10.1097/FTD.0b013e3181838063. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Miura M, Kagaya H, Satoh S, Inoue K, Saito M, Habuchi T, Suzuki T: Influence of drug transporters and UGT polymorphisms on pharmacokinetics of phenolic glucuronide metabolite of mycophenolic acid in Japanese renal transplant recipients. Ther Drug Monit. 2008 Oct;30(5):559-64. doi: 10.1097/FTD.0b013e3181838063. [Article]
- Wang J, Figurski M, Shaw LM, Burckart GJ: The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice. Transpl Immunol. 2008 Jul;19(3-4):192-6. doi: 10.1016/j.trim.2008.05.009. Epub 2008 Jun 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Wang J, Figurski M, Shaw LM, Burckart GJ: The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice. Transpl Immunol. 2008 Jul;19(3-4):192-6. doi: 10.1016/j.trim.2008.05.009. Epub 2008 Jun 18. [Article]
- Kobayashi M, Saitoh H, Kobayashi M, Tadano K, Takahashi Y, Hirano T: Cyclosporin A, but not tacrolimus, inhibits the biliary excretion of mycophenolic acid glucuronide possibly mediated by multidrug resistance-associated protein 2 in rats. J Pharmacol Exp Ther. 2004 Jun;309(3):1029-35. doi: 10.1124/jpet.103.063073. Epub 2004 Feb 20. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:04